Human Flu Viruses Research Articles

SARS-CoV-2 and animals, a long story that doesn't have to end now: What we need to learn from the emergence of the Omicron variant.

OIE, the world organization for animal health, recently released an update on the state of the art of knowledge regarding SARS-CoV-2 in animals. For farmed animals, ferrets and minks were found to be highly susceptible to the virus and develop symptomatic disease both in natural conditions and in experimental infections. Lagomorphs of the species Oryctolagus cuniculus are indicated as highly susceptible to the virus under experimental conditions, but show no symptoms of the disease and do not transmit the virus between conspecifics, unlike raccoon dogs (Nyctereutes procyonoides), which in addition to being highly susceptible to the virus under experimental conditions, can also transmit the virus between conspecifics. Among felines, the circulation of the virus has reached a level of cases such as sometimes suggests the experimental use of vaccines for human use or treatments with monoclonal antibodies. But even among wild animals, several species (White-tailed deer, Egyptian rousettes, and minks) have now been described as potential natural reservoirs of the virus. This proven circulation of SARS-CoV-2 among animals has not been accompanied by the development of an adequate surveillance system that allows following the evolution of the virus among its natural hosts. This will be all the more relevant as the surveillance system in humans inevitably drops and we move to surveillance by sentinels similar to the human flu virus. The lesson that we can draw from the emergence of Omicron and, more than likely, its animal origin must not be lost, and in this mini-review, we explain why.

The matrix gene of pdm/09 H1N1 contributes to the pathogenicity and transmissibility of SIV in mammals

The H1N1 influenza virus of swine-origin was responsible for the H1N1 pandemic in 2009 (pdm/09 H1N1), where the virus was transmitted to humans and then spread between people, and its continued circulation has resulted in it becoming a seasonal human flu virus. Since 2016, the matrix (M) gene of pdm/09 H1N1 has been involved in the reassortment of swine influenza viruses (SIVs) in China and has gradually become a dominant genotype in pigs. However, whether M gene substitution will influence the fitness of emerging SIVs remains unclear. Here, we analyzed the biological characteristics of SIVs with the M gene from Eurasian avian-like (EA) SIV or pdm/09 H1N1 in mammals and found that SIVs containing the pdm/09-M gene exhibit stronger virulence in mice, more efficient respiratory droplet transmission between ferrets, and increased transcription of viral genes in A549 cells compared with those containing EA-M. We also determined the functional significance of the pdm/09-M gene in conferring an elevated release of progeny viruses comprised of largely filamentous virions rather than spherical virions. Our study suggests that pdm/09-M plays a crucial role in the genesis of emerging SIVs in terms of the potential prevalence in the population.

Synthesis of C5-C6 Derivatives of 1,3-Dimethyl-5-Fluorouracil and 5-Fluorouracil. Screening for Antiviral Activity

5-Chloro-5-fluoro-6-alkoxypyrimidines were synthesized via Cl2 chlorination of 5-fluorouracil and 1,3-dimethyl-5-fluorouracil in various alcohols and were screened for antiviral activity. High antiviral activity was found for 5-chloro-5-fluoro-6-hydroxy-5,6-dihydrouracil against RS virus and human flu viruses A/H3N2 and A/H1N1pdm09.

Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs

Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract.

Sorption of Flu Viruses from Aqueous Media by Composites of Electrically Conducting Polymers: Polyaniline and Polypyrrole

Composites of polymers with conjugated chain structures, polyaniline and polypyrrole, are used as sorbents for human and bird flu viruses. Sorption properties of the composites are compared to characteristics of the initial polymers. It is shown that polymer composites containing metallic silver nanoparticles possess sorption activity, similarly to their composites with polyethylene and the initial polyaniline and polypyrrole. The introduction of silver into polypyrrole resulted in an enhancement of the sorption activity as compared to that of the initial polymer. Nontoxic metal—polymer composites reduce considerably the concentrations of human flu viruses A(H1N1), A(H3N2), and B and bird flu virus A(H5N2) with different structures of surface virion proteins in aqueous media at a sorbent concentration of 10–20 mg/mL in the temperature range from +4 to 37°C.

Post-pandemic seroprevalence of human influenza viruses in domestic cats.

The continuous exposure of cats to diverse influenza viruses raises the concern of a potential role of cats in the epidemiology of these viruses. Our previous seroprevalence study of domestic cat sera collected during the 2009 H1N1 pandemic wave (September 2009–September 2010) revealed a high prevalence of pandemic H1N1, as well as seasonal H1N1 and H3N2 human flu virus infection (22.5%, 33.0%, and 43.5%, respectively). In this study, we extended the serosurvey of influenza viruses in cat sera collected post-pandemic (June 2011–August 2012). A total of 432 cat sera were tested using the hemagglutination inhibition assay. The results showed an increase in pandemic H1N1 prevalence (33.6%) and a significant reduction in both seasonal H1N1 and H3N2 prevalence (10.9% and 17.6%, respectively) compared to our previous survey conducted during the pandemic wave. The pandemic H1N1 prevalence in cats showed an irregular seasonality pattern in the post-pandemic phase. Pandemic H1N1 reactivity was more frequent among female cats than male cats. In contrast to our earlier finding, no significant association between clinical respiratory disease and influenza virus infection was observed. Our study highlights a high susceptibility among cats to human influenza virus infection that is correlated with influenza prevalence in the human population.

Conformation and Linkage Studies of Specific Oligosaccharides Related to H1N1, H5N1, and Human Flu for Developing the Second Tamiflu.

The interaction between viral HA (hemagglutinin) and oligosaccharide of the host plays an important role in the infection and transmission of avian and human flu viruses. Until now, this interaction has been classified by sialyl(α2-3) or sialyl(α2-6) linkage specificity of oligosaccharide moieties for avian or human virus, respectively. In the case of H5N1 and newly mutated flu viruses, classification based on the linkage type does not correlate with human infection and human-to-human transmission of these viruses. It is newly suggested that flu infection and transmission to humans require high affinity binding to the extended conformation with long length sialyl(α2-6)galactose containing oligosaccharides. On the other hand, the avian flu virus requires folded conformation with sialyl(α2-3) or short length sialyl(α2-6) containing trisaccharides. This suggests a potential future direction for the development of new species-specific antiviral drugs to prevent and treat pandemic flu.

The influenza enigma

To disease detectives at the world's leading public health agencies, influenza is an all-too familiar foe. First isolated in 1932, the virus--a single-stranded member of the orthomyxovirus family--occurs every year in every country, seasonally and sporadically, killing between 250 000 and 500 000 people and causing severe illness in several million more, according to the World Health Organization (WHO). Over the past three centuries, there have been at least 10 global influenza pandemics and three in the last century alone, among them the so-called 'Spanish flu' of 1918-1919. The single most devastating disease outbreak in human history, that pandemic is believed to have caused between 20 million and 50 million deaths worldwide. It is the prospect of another such catastrophe, and the staggering toll of seasonal flu, that has made influenza the world's second-most studied virus, behind HIV. In recent years, those investments in influenza research have yielded important new insights about the virus's genetic makeup and capacity for mutation. Indeed, with the reconstruction of the 1918 virus at the US Centers for Disease Control and Prevention (CDC) in Atlanta in 2005, scientists were able to identify the genetic changes that allowed the virus to cross the species barrier between birds and humans, confirming fears that the avian H5N1 strain that has been circulating in Asia could one day do the same. [ILLUSTRATION OMITTED] Now, at two leading influenza laboratories at the University of Wisconsin-Madison, in the United States of America (USA) and Erasmus MC in Rotterdam, the Netherlands, researchers have broken new ground by creating mutant H5N1 strains. The controversial studies, which have been paused for a debate over the risks they may pose to public health, demonstrate that viruses equipped with a haemagglutinin protein from highly pathogenic H5N1 viruses can become transmissible in ferrets. Ferrets are believed to be the ideal small animal model for influenza because they are susceptible to human flu viruses and some of the symptoms seen in humans. It is not yet known whether this mutant H5N1 is transmissible in humans and a study to find that out would probably not be possible. But we can infer that there is a high likelihood of transmissibility based on the findings in ferrets. Yet for all of the advances afforded by new genomic technologies, our understanding of the fundamental epidemiology of influenza remains far from complete. Such broad questions as what specific forces direct the appearance and disappearance of epidemics still challenge virologists and epidemiologists, wrote the late, long-serving CDC epidemiologist Michael Gregg in 1980. This is still the case today. Take, for example, the enduring enigma of influenza seasonality. The clock-like consistency of the virus's winter incidence, which peaks in temperate zones, provides perhaps the most striking illustration of seasonality in infectious diseases. However, clouding the picture is the highly variable pattern of seasonal flu outbreaks in the tropics, says US National Institutes of Health (NIH) epidemiologist Martha Nelson. They can be associated with rainy seasons or dry seasons, and you could have one epidemic or two she says. It's really not well understood. This despite several untested and inconclusive theories being put forward as to why this is the case. Similarly puzzling is the question of where those seasonal strains come from. Although it has long been held that south-east and eastern Asia are the global source of seasonal flu epidemics, a recent study by researchers at the Duke-National University of Singapore (NUS) Graduate Medical School casts considerable doubt on that assumption. Published last November in the journal Proceedings of the National Academy of Sciences, the study compared viral migration between urban centres in seven different temperate and tropical regions between 2003 and 2006. …

Simulation of Swine and Avian Influenza Viruses Recombination Based on Genetic Algorithm

This paper describes analysis, design and development of simulation software for Swine (H1N1) and Avian Influenza (H5N1) viruses recombination process. Influenza Pandemics have occurred several times, caused by mutation and recombination of Influenza viruses. Recombination is a sudden change of viruses enabling two different Influenza virus strains combined to become a new virus subtype. The H1N1 recombination has caused Spanish Flu Pandemic in 1918, and the recombination of swine virus, human virus and bird virus has caused Swine Flu Pandemic started in Mexico during April 2009. The main concern raised by WHO is the possibility of recombination between Swine Flu (H1N1), Avian Flu (H5N1) and Human Flu Virus (H3N2) which could trigger Swine Flu becomes more contagious, and have a higher CFR (Case Fatality Rate) causing more people to die. This research's purpose is to define modeling for virus recombination causing Influenza Pandemic phenomena. This research defines several different virus variants which can potentially trigger the Influenza Pandemic. Additionally, this simulation objective is to obtain most possible virus strains formed from the recombination, the scope within this article, which can potentially trigger Influenza Pandemic. New strains could be utilized to support the vaccine planning process. This simulation program was developed based on Genetic Algorithm method, for solving this multi-objective optimization problem. By utilizing Genetic Algorithm approach, the chromosome solution and fitness values/functions of Influenza Pandemic stages are defined and the maximum fitness values are to be searched. The simulation result of H1N1 and H5N1 recombination gave 2 best fitness values as static result and dynamic mean fitness values. Better and more fitness values could be obtained once the database of recombination and mutation virus strains is enhanced.

Pandemic Influenza A (H1N1) Virus (“Swine Flu”) Probably Is More Virulent Than Seasonal Flu Virus

A Japanese team has examined whether pandemic influenza A (H1N1) virus is more virulent than a widely circulating seasonal H1N1 human flu virus. The

Computational studies of H5N1 hemagglutinin binding with SA-α-2, 3-Gal and SA-α-2, 6-Gal

For influenza H5N1 hemagglutinin, a switch from SA-α-2, 3-Gal to SA-α-2, 6-Gal receptor specificity is a critical step leading to the conversion from avian-to-human to human-to-human infection. Therefore, the understanding of the binding modes of SA-α-2, 3-Gal and SA-α-2, 6-Gal to H5N1 hemagglutinin will be very important for the examination of possible mutations needed for going from an avian to a human flu virus. Based on the available H5N1 hemagglutinin crystal structure, the binding profiles between H5N1 hemagglutinin and two saccharide ligands, SA-α-2, 3-Gal and SA-α-2, 6-Gal, were investigated by ab initio quantum mechanics, molecular docking, molecular mechanics, and molecular dynamics simulations. It was found that SA-α-2, 3-Gal has strong multiple hydrophobic and hydrogen bond interactions in its trans conformation with H5N1 hemagglutinin, whereas the SA-α-2, 6-Gal only shows weak interactions in a different conformation (cis type).

Growing Threat of a Bird Flu Pandemic

Some influenza viruses that normally reside in birds can recombine with human flu viruses and spread among humans. Such an event triggered the

Human influenza surveillance in areas with animal flu epidemics and China visitors in Taiwan

Background: This study investigates the changes in human flu viruses in areas where unique animal flu viruses or epidemics were isolated in Taiwan and Kinmen islet. Materials and methods: Sentinel physicians obtained throat swabs from patients presenting with flu-like illness and two-step RT-PCR, using five sets of primers for matrix (M) and HA2, to detect all the animal influenza viruses and then typing/subtyping for human flu viruses. Questionnaires included travel history, animal contacts and occupations. Results: One flu B and eight flu A H3N2 isolates were identified in the flu season of 2002–2003, including 1, 2, 2 and 3 H3N2 in Taoyuan, Yilan, Tainan and Kinmen, respectively. Amino acid sequences of HA of human isolates revealed that Pro (P) at position 227 among most of the Kinmen isolates (2/3) replaced Ser (S) in the Taiwanese isolates, including one mutant from Gln (Q) to His (H) at position 156 of the HA gene for five out of eight H3N2 Taiwan isolates. Phylogenetic analysis demonstrated that all of the H3N2 viruses were of human origin (belonging to the lineage of A/Fujian/411/2002), with 80–90% homology in HA, NA and M gene segments of A/Swine/PingTung/Taiwan/199.2/02 (H3N2) and 75–77% homology in HA gene segment of A/Wild Bird/Taiwan/243/02(H3) and A/Mallard Duck/Taiwan/3.3/03 (H3). Conclusions: Residents in Kinmen islet frequently traveling from China need to monitor their flu A viruses that might be different from those obtained on the main Taiwan island.